{
  "abstract": "Background Antitopoisomerase I (ATA), anticentromere (ACA) and anti-RNA polymerase III (RNAP3) antibodies are included in the 2013 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for systemic sclerosis (SSc). A subset of patients with SSc satisfy criteria but may lack these specific autoantibodies, being classified as ‘triple-negative’.Methods We conducted a retrospective evaluation of triple-negative patients with SSc prevalence and clinical features among the multicentric Systemic sclerosis Progression INvestiGation registry.Results Out of 1480 patients with SSc, 295 (19.9%) were triple-negative, while 1185 (81.1%) had SSc-specific antibodies: ACA (54.3%), ATA (43.6%) and RNAP3 (2.1%). The triple-negative group showed a higher prevalence of myopathy (16.7% vs 10.1%, p=0.003), suggested by higher creatine phosphokinase (CPK) levels (126.2 vs 92.5 U/mL, p=0.002), more frequent CPK increase over 2–3 times (2.4% vs 0.2%, p=0.028). Triple-negative patients also exhibited fewer vascular complications, including digital ulcers (17.3% vs 22.8%, p=0.04) and calcinosis (8.2% vs 12.8%, p=0.027), and a higher prevalence of interstitial lung disease (p<0.001). Consistently, lower diffusing capacity for carbon monoxide (66.4% vs 70.98%, p=0.004) and forced vital capacity (97.01% vs 102.92%, p<0.001) were found in the triple-negative group. Triple-negative patients more frequently received corticosteroids (79.3% vs 67.9%, p=0.003), cyclophosphamide (43.4% vs 26%, p<0.001) and azathioprine (38.5% vs 22.3%, p=0.002), while less frequently received prostanoids (71.6% vs 85.9%, p<0.001), calcium channel blockers (80.1% vs 87.7%, p=0.005) and phosphodiesterase-5 inhibitors (4% vs 20%, p<0.001).Conclusions A higher prevalence of myopathy and interstitial lung disease and a reduced vascular burden were found in the triple-negative patients, suggesting that the non-specific and non-routinely tested autoantibodies may identify an SSc endotype resembling sclero-myositis.",
  "authors": [
    {
      "affiliations": [
        "Vita-Salute San Raffaele University, Milan, Italy",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milan, Italy",
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Veronica Batani"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, ASST Spedali Civili of Brescia, Brescia, Italy",
        "Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"
      ],
      "name": "Ilaria Cavazzana"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Martina Orlandi"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy"
      ],
      "name": "Rossella De Angelis"
    },
    {
      "affiliations": [
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milan, Italy"
      ],
      "name": "Corrado Campochiaro"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Enrico De Lorenzis"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Gerlando Natalello"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Lucrezia Verardi"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia and University of Modena and Reggio Emilia, Reggio Emilia, Italy"
      ],
      "name": "Gianluigi Bajocchi"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy",
        "Division of Rheumatology Scleroderma Unit, AOUC, University of Florence, Florence, Italy"
      ],
      "name": "Silvia Bellando-Randone"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy",
        "Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy"
      ],
      "name": "Giovanni Zanframundo"
    },
    {
      "affiliations": [
        "Rheumatology Unit, A.O.U Policlinico S. Marco, Catania, Italy"
      ],
      "name": "Rosario Foti"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Precision and Regenerative Medicine and Jonic Area, University of Bari, Bari, Italy",
        "Department of Medicine and Surgery, LUM University “Giuseppe De Gennaro” Casamassima & Rheumatology Service “Miulli” General Hospital Acquaviva delle Fonti, Bari, Italy"
      ],
      "name": "Fabio Cacciapaglia"
    },
    {
      "affiliations": [
        "Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Caserta, Italy"
      ],
      "name": "Giovanna Cuomo"
    },
    {
      "affiliations": [
        "Department of Medicine, Internal Medicine and Rheumatology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy"
      ],
      "name": "Alarico Ariani"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "Edoardo Rosato"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"
      ],
      "name": "Gemma Lepri"
    },
    {
      "affiliations": [
        "Department of Medicine, Rheumatology Unit, Ospedale GB Morgagni–L Pierantoni, Forlì, Italy"
      ],
      "name": "Francesco Girelli"
    },
    {
      "affiliations": [
        "Department of Clinical, Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "Valeria Riccieri"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Padua, Padua, Italy"
      ],
      "name": "Elisabetta Zanatta"
    },
    {
      "affiliations": [
        "Clinical Rheumatology Unit, ASST Gaetano Pini-CTO, Department of Clinical Sciences & Community Health, Dipartimento di Eccellenza 2023-2027, Università degli Studi di Milano, Milan, Italy"
      ],
      "name": "Francesca Ingegnoli"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy",
        "Humanitas University, Pieve Emanuele, Italy"
      ],
      "name": "Maria De Santis"
    },
    {
      "affiliations": [
        "Research Hospital San Martino, University of Genoa, Genoa, Italy"
      ],
      "name": "Giuseppe Murdaca"
    },
    {
      "affiliations": [
        "Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital, Potenza, Italy"
      ],
      "name": "Giuseppina Abignano"
    },
    {
      "affiliations": [
        "Azienda Ospedaliera S Croce e Carle, Cuneo, Italy"
      ],
      "name": "Pettiti Giorgio"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Pisa, Pisa, Italy"
      ],
      "name": "Alessandra Della Rossa"
    },
    {
      "affiliations": [
        "Departmental Rheumatology Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy"
      ],
      "name": "Maurizio Caminiti"
    },
    {
      "affiliations": [
        "Rheumatology Unit, San Camillo–Forlanini Hospital, Roma, Italy"
      ],
      "name": "Anna Maria Iuliano"
    },
    {
      "affiliations": [
        "Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy"
      ],
      "name": "Lorenzo Beretta"
    },
    {
      "affiliations": [
        "Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"
      ],
      "name": "Gianluca Bagnato"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Molise, Campobasso, Italy"
      ],
      "name": "Ennio Lubrano"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda Ospedaliera di Rilievo Nazionale ed Alta Specializzazione “Garibaldi”, Catania, Italy"
      ],
      "name": "Ilenia De Andres"
    },
    {
      "affiliations": [
        "Rheumatology Section, Department of Medicine, University of Verona, Verona, Italy"
      ],
      "name": "Luca Idolazzi"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy"
      ],
      "name": "Cosimo Bruni"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Precision and Regenerative Medicine and Jonic Area, University of Bari, Bari, Italy"
      ],
      "name": "Marco Fornaro"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Mauriziano-Umberto I Hospital, Torino, Italy"
      ],
      "name": "Marta Saracco"
    },
    {
      "affiliations": [
        "San Lorenzo Hospital, Carmagnola, Italy"
      ],
      "name": "Cecilia Agnes"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Clinical and Molecular Sciences, Polytechnic University of Marche, Ancona, Italy"
      ],
      "name": "Edoardo Cipolletta"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Federica Lumetti"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Amelia Spinella"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Marco De Pinto"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"
      ],
      "name": "Luca Magnani"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy"
      ],
      "name": "Veronica Codullo"
    },
    {
      "affiliations": [
        "Department of Medicine and Surgery, LUM University “Giuseppe De Gennaro” Casamassima & Rheumatology Service “Miulli” General Hospital Acquaviva delle Fonti, Bari, Italy"
      ],
      "name": "Elisa Visalli"
    },
    {
      "affiliations": [
        "Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Caserta, Italy"
      ],
      "name": "Carlo Iandoli"
    },
    {
      "affiliations": [
        "Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy"
      ],
      "name": "Antonietta Gigante"
    },
    {
      "affiliations": [
        "IRCCS Ospedale Galeazzi Sant’Ambrogio, Milan, Italy",
        "Dipartimento di Scienze Biomediche e Cliniche, University of Milan, Milan, Italy"
      ],
      "name": "Greta Pellegrino"
    },
    {
      "affiliations": [
        "Medicine Unit, Azienda Pedemontana 7, Ospedale San Bassiano, Bassano del Grappa, Italy"
      ],
      "name": "Erika Pigatto"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, ASST Spedali Civili of Brescia, Brescia, Italy",
        "Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"
      ],
      "name": "Maria-Grazia Lazzaroni"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, ASST Spedali Civili of Brescia, Brescia, Italy",
        "Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy"
      ],
      "name": "Franco Franceschini"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy",
        "Humanitas University, Pieve Emanuele, Italy"
      ],
      "name": "Francesca Motta"
    },
    {
      "affiliations": [
        "Rheumatology and Clinical Immunology, IRCCS Humanitas Research Hospital, Rozzano, Italy",
        "Humanitas University, Pieve Emanuele, Italy"
      ],
      "name": "Antonio Tonutti"
    },
    {
      "affiliations": [
        "Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital, Potenza, Italy"
      ],
      "name": "Gianna Mennillo"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Pisa, Pisa, Italy"
      ],
      "name": "Marco Di Battista"
    },
    {
      "affiliations": [
        "Departmental Rheumatology Unit, Grande Ospedale Metropolitano, Reggio Calabria, Italy"
      ],
      "name": "Giuseppa Pagano Mariano"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medical Sciences, University of Ferrara, Ferrara, Italy",
        "Azienda Ospedaliera-Universitaria S. Anna di Ferrara, Ferrara, Italy"
      ],
      "name": "Federica Furini"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medical Sciences, University of Ferrara, Ferrara, Italy",
        "Azienda Ospedaliera-Universitaria S. Anna di Ferrara, Ferrara, Italy"
      ],
      "name": "Licia Vultaggio"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy"
      ],
      "name": "Simone Parisi"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy"
      ],
      "name": "Clara Lisa Peroni"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Musculoskeletal Sciences, Local Health Trust La Colletta Hospital, Genova, Italy"
      ],
      "name": "Gerolamo Bianchi"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Torino, Italy"
      ],
      "name": "Enrico Fusaro"
    },
    {
      "affiliations": [
        "Rheumatology Unit, San Camillo–Forlanini Hospital, Roma, Italy"
      ],
      "name": "Gian Domenico Sebastiani"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Department of Medical Sciences, University of Ferrara, Ferrara, Italy",
        "Azienda Ospedaliera-Universitaria S. Anna di Ferrara, Ferrara, Italy"
      ],
      "name": "Marcello Govoni"
    },
    {
      "affiliations": [
        "Rheumatology Institute of Lucania (IReL) and Rheumatology Department of Lucania, San Carlo Hospital, Potenza, Italy"
      ],
      "name": "Salvatore D’Angelo"
    },
    {
      "affiliations": [
        "Department of Medicine, Villa Salus Hospital, Venice, Italy"
      ],
      "name": "Franco Cozzi"
    },
    {
      "affiliations": [
        "Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy",
        "Division of Rheumatology Scleroderma Unit, AOUC, University of Florence, Florence, Italy"
      ],
      "name": "Serena Guiducci"
    },
    {
      "affiliations": [
        "Department of Rheumatology, University of Padua, Padua, Italy"
      ],
      "name": "Andrea Doria"
    },
    {
      "affiliations": [
        "Rheumatology Unit, Azienda USL-IRCCS di Reggio Emilia and University of Modena and Reggio Emilia, Reggio Emilia, Italy"
      ],
      "name": "Carlo Salvarani"
    },
    {
      "affiliations": [
        "Rheumatology Unit, A.O.U Policlinico S. Marco, Catania, Italy"
      ],
      "name": "Florenzo Iannone"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Maria Antonietta D’Agostino"
    },
    {
      "affiliations": [
        "Division of Rheumatology, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy"
      ],
      "name": "Silvia Laura Bosello"
    },
    {
      "affiliations": [
        "Vita-Salute San Raffaele University, Milan, Italy",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milan, Italy"
      ],
      "name": "Lorenzo Dagna"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Dilia Giuggioli"
    },
    {
      "affiliations": [
        "Rheumatology Unit, School of Medicine, University of Modena and Reggio Emilia, Modena, Italy"
      ],
      "name": "Clodoveo Ferri"
    },
    {
      "affiliations": [
        "Vita-Salute San Raffaele University, Milan, Italy",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milan, Italy"
      ],
      "name": "Marco Matucci Cerinic"
    },
    {
      "affiliations": [
        "Vita-Salute San Raffaele University, Milan, Italy",
        "Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), Inflammation, Fibrosis and Ageing Initiative (INFLAGE), IRCCS Ospedale San Raffaele, Milan, Italy"
      ],
      "name": "Giacomo De Luca"
    },
    {
      "affiliations": [],
      "name": "On the behalf of SPRING collaborators"
    }
  ],
  "title": "Clinical and serological features of triple autoantibody-negative patients with systemic sclerosis: insights from the multicentric SPRING registry of the Italian Society for Rheumatology",
  "uid": "180beb7b-d9f9-5bbd-88a2-a33fef82d301"
}